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Randomized Controlled Trial
. 2025 Jan 28;104(2):e209871.
doi: 10.1212/WNL.0000000000209871. Epub 2024 Dec 20.

Effect of IV Thrombolysis With Alteplase in Patients With Vessel Occlusion in the WAKE-UP Trial

Ivana Galinovic  1 , Jochen B Fiebach  1 , Florent Boutitie  1 , Bastian Cheng  1 , Tae-Hee Cho  1 , Martin Ebinger  1 , Matthias Endres  1 , Christian Enzinger  1 , Jens Fiehler  1 , Ian Ford  1 , Johannes Gregori  1 , Matthias Günther  1 , Robin Lemmens  1 , Keith W Muir  1 , N Nighoghossian  1 , Pascal Roy  1 , Claus Z Simonsen  1 , Vincent N Thijs  1 , Anke Wouters  1 , Christian Gerloff  1 , Götz Thomalla  1 , Salvador Pedraza  1 ; for WAKE-UP Investigators  1
Collaborators, Affiliations
Randomized Controlled Trial

Effect of IV Thrombolysis With Alteplase in Patients With Vessel Occlusion in the WAKE-UP Trial

Ivana Galinovic et al. Neurology. .

Abstract

Background and objectives: Data from randomized trials on the treatment effect of pure thrombolysis in patients with vessel occlusion are lacking. We examined data from a corresponding subsample of patients from the multicenter, randomized, placebo-controlled WAKE-UP trial to determine whether MRI-guided IV thrombolysis with alteplase in unknown-onset ischemic stroke benefits patients presenting with vessel occlusion.

Methods: Patients with an acute ischemic lesion visible on MRI diffusion-weighted imaging but no marked parenchymal hyperintensity on fluid-attenuated inversion recovery images were randomized to treatment with IV alteplase or placebo. The primary end point was a favorable outcome defined by a modified Rankin Scale score of 0-1 at 90 days after stroke. We investigated the interaction between vessel status and treatment effect using an unconditional logistic regression model. Treatment effects (adjusted odds ratio [aOR]) and their 95% CI were compared in patients with and without any vessel occlusion (AVO) and large vessel occlusion (LVO).

Results: 185 patients (mean age 64.5 years, 46% female, median NIH Stroke Scale score 9, median time between last seen well and MRI 10.26 hours) received treatment and presented with an occlusion. 98 (20%) had LVO (defined as occlusion of the internal carotid artery, middle cerebral artery trunk, or combination). A favorable outcome was observed in 30 of 94 patients with AVO (31.9%) in the alteplase group and in 18 of 91 (19.8%) in the placebo group (aOR 2.04, 95% CI 1.00-4.18). In the subgroup of patients with LVO, a favorable outcome was observed in 16 of 53 (30.2%) in the alteplase group and in 7 of 44 (15.9%) in the placebo group (aOR 2.08, 95% CI 0.71-6.10). Treatment with alteplase was associated with higher odds of favorable outcomes with no heterogeneity of treatment effect between patients with AVO and patent vessel (p = 0.56), or between patients with and without LVO (p = 0.69).

Discussion: Although the WAKE-UP study was not powered to demonstrate treatment efficacy in patient subpopulations, this subgroup analysis points to a benefit of MRI-guided thrombolysis in patients with unknown-onset ischemic stroke, independent of vessel occlusion.

Clinical trial registration: Registered at ClinicalTrials.gov with unique identifier NCT01525290 (clinicaltrials.gov/study/NCT01525290). The study was first posted on February 2, 2012; the first patient was enrolled on September 24, 2012.

Classification of evidence: This study provides Class II evidence that for patients with unknown-onset ischemic stroke with AVO, MRI-guided treatment with IV tissue plasminogen activator improves outcomes.

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Conflict of interest statement

I. Galinovic and J.B. Fiebach report grants from European Union 7th Framework Program during the conduct of the study. F. Boutitie reports grants from University Medical Center Hamburg-Eppendorf during the conduct of the study. B. Cheng reports grants from European Union 7th Framework Program during the conduct of the study. T.-H. Cho reports no disclosures relevant to the manuscript. M. Ebinger reports grants from European Union 7th Framework Program during the conduct of the study. M. Endres, C. Enzinger, J. Fiehler, I. Ford, J. Gregori, M. Günther, and R. Lemmens report no disclosures relevant to the manuscript. K.W. Muir reports grants from European Union 7th Framework Program during the conduct of the study. N. Nighoghossian, P. Roy, and C.Z. Simonsen report no disclosures relevant to the manuscript. V. Thijs reports grants from European Union 7th Framework Program during the conduct of the study. A. Wouters reports no disclosures relevant to the manuscript. C. Gerloff, G. Thomalla, and S. Pedraza report grants from European Union 7th Framework Program during the conduct of the study. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Forest Plots Depicting the Effect of Alteplase on Favorable Outcomes in Patients With Initial Vessel Occlusion
*p Value is the test of interaction between treatment and each subgroup. OR = odds ratio.
Figure 2
Figure 2. Distribution of Scores on the Modified Rankin Scale at 90 Days
AVO = any vessel occlusion; LVO = large vessel occlusion.
See this image and copyright information in PMC

References

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